Histones, which are basic nucleoproteins believed to be involved in genetic repression and control, have been found to be abnormal in the group of malignant disorders of erythropoiesis known as the DiGuglielmo syndrome. These disorders include acute and chronic erythremic myelosis, erythroleukemia and refractory sideroblastic anemia. The ways in which these histone abnormalities arise and how they contribute to the pathogenesis of the malignant erythroid precursors and to the acute leukemias which often evolve from them are unknown. In this proposal, studies of malignant erythroid and leukemic nucleoproteins (DNA, DN- protein, and histone) utilizing high resolution electron microscopy, viscosity studies and differential staining of DNA and histones have been described. By helping to elucidate the spatial orientation of histone along DNA strands, these studies may facilitate the understanding of the pathogenesis of the megaloblastoid chromatin pattern found in the malignant erythroid precursors. Additional studies relating to the cytochemical determination of methyltransferase enzymes may aid in the understanding of the pathogenesis of the methylated arginines found in the erythroid histones of the DiGuglielmo syndrome.